Evidence for epigenetic regulation playing a role in Parkinson’s disease (PD) is growing, particularly for DNA methylation. Approximately 90% of PD cases are due to a complex interaction between age, genes, and environmental factors, and epigenetic marks are thought to mediate the relationship between aging, genetics, the environment, and disease risk. To date, there are a small number of published genome-wide studies of DNA methylation in PD, but none accounted for cell type or sex in their analyses. Given the heterogeneity of bulk brain tissue samples and known sex differences in PD risk, progression, and severity, these are critical variables to account for. In this genome-wide analysis of DNA methylation in an enriched neuronal population from PD postmortem parietal cortex, we report sex-specific PD-associated methylation changes in PARK7 (DJ-1), SLC17A6 (VGLUT2), PTPRN2 (IA-2β), NR4A2 (NURR1), and other genes involved in developmental pathways, neurotransmitter packaging and release, and axon and neuron projection guidance.

表观遗传调控在帕金森病 (PD) 中发挥作用的证据越来越多，尤其是 DNA 甲基化。大约 90% 的 PD 病例是由于年龄、基因和环境因素之间复杂的相互作用造成的，表观遗传标记被认为可以调节衰老、遗传、环境和疾病风险之间的关系。迄今为止，有少量已发表的 PD DNA 甲基化全基因组研究，但没有一项在其分析中考虑细胞类型或性别。鉴于大量脑组织样本的异质性以及已知的 PD 风险、进展和严重程度的性别差异，这些都是需要考虑的关键变量。在这项对来自 PD 死后顶叶皮层的丰富神经元群体中 DNA 甲基化的全基因组分析中，我们报告了性别特异性 PD 相关的甲基化变化PARK7 (DJ-1)、SLC17A6 (VGLUT2)、PTPRN2 (IA-2β)、NR4A2 (NURR1) 和其他参与发育途径、神经递质包装和释放以及轴突和神经元投射引导的基因。